Yawning behavior is a curious and still
little-understood phenomenon that is displayed
in many vertebrate species. Despite the great
sociobiological importance and extraordinarily
widespread incidence of yawning, this
stereotyped behavior bas been the subject of
very little empirical research. The behavior, if
practiced in excess, may be a sign of diseases
such as chorea, brain tumors, or encephalitis.

Most rats normally show one to two
episodes of yawning per hour. They are
usually sleepy during the time of yawning, but
yawning can be elicited in experimental animals
by the cholinergic agents physostigmine and
pilocarpine, which is inhibited by muscarinic
blockade. Considerable interest bas developed in
a yawning syndrome that is produced by
dopamine agonists in rats. The paraventricular
nucleus, incerto-hypothalamic dopamine system,
and septal and striatal dopamine receptors have
A been suggested to mediate yawning in rats. The
behavior scems to be mediated through D2
dopamine receptors. Central cholinergic
mechanisms mediate the yawning induced by
dopamine receptor agonists, and the response is
inhibited by muscarir& antagonists such as
scopolamine and atropine.

The influences of GABAergic agents, adenosine
receptor agents and opioidergic agents on
cholinergicinduced yawning have been
investigated in our previous work. There is
evidence that the adrenceptor system may
influence some behaviors in rats. In the present
study, effects of adrenoceptor mechanism(s) on
physostigmine-induced yawning were studied.
[...]

DISCUSSION

In this work, the influence of adrenoceptor
agonists and antagonists on
physostigmine-induced yawning were investigated.
Previous studies have shown that cholinergie or
dopamine D2 receptor activation induce yawning.
The behavior induced by cholinoceptor agents is
antagonized by muscarinic receptor antagonists
but not by dopaminergic receptor antagonists,
and behavior induced by dopamine D, receptor
agonists is inhibited by both dopaminergic and
muscarmie receptor antagonists. These data imply
that the yawning induced by cholinoceptor agents
involves activation of cholinergic neuronal
mechanism(s), and the yawning induced by
dopaminergic receptor agonists appears to be
mediated via activation of dopaminergic and
cholinergic mechanisms. The yawning can also be
influenced by different systems (e.g., dopaminc
D1 receptor stimulation; opiodergic, GABAergic
and adenosine mechanisms). Together with
evidence for the role of dopaminergic,
cholinergic, and other mechanisms in mediating
yawning, evidence also indicates an important
modulatory role for the noradrenergic
system.

The present results show that intraperitoneal
(IP) injection of the cholinesterase inhibitor,
physostigmine, induced dosedependent yawning.
The response was maximal with 0.2 mg/ kg of the
drug. This is in agreement with previous work
that found that activation of the cholinergic
mechanism may induce yawning. The present data
indicate that administration of the
alpha2-adrenoceptor agonist. phenylephrine, and
the alpha2-adrenoceptor agonist, clonidine,
decreased physostigmine's effect. Therefore, it
can be suggested that adrenergic system(s) is
involved in the present response. This may be in
agreement with other reports that indicate that
adrenoceptor mechanisms may influence some of
the behaviors in rats. The effect induced by
phenylephrine can be decreased by the
alpha1-adrenoceptor antagonist, prazosin, which
may show that inhibition of the yawning induced
by phenylephrine is mediated through an
alpha1-adrenoceptor mechanism. This is not
consistent with data obtained by some authors
who showed that physostigmine-induced yawning
could not be affected by alpha1-adrenoceptors.
The higher dose of the alpha2-adrenoceptor
antagonist, yohimbine, also reduced the
inhibition induced by clonidine. The possibility
may exist that clonidine produces its effect
through alpha2-receptor activity. This is in
agreement with results obtained by some
investigators who showed clonidine could reduce
cholinergic-induced yawning. Because low doses
of yohimbine by itself reduced
physostigmine-induced yawning, receptor blockade
by the alpha2-receptor antagonist cannot be
shown. Thus, low doses of yohimbine may block
et, presynaptic adrenoceptors and, in turn, may
release noradrenaline. The released
neurotransmitter may cause inhibition of
physostigmine's response through activation of
adrenoceptors. However, prazosin administration
could not reduce the yohimbine influence on
physostigmine-induced yawning.

Evidence also exists that alpha2-adrenoceptor
activation may decrease dopamine release.
Therefore, there may be a possibility that
blockade alpha2-adrenoceptor by yohimbine
releases dopamine. Stimulation of D1 dopamine
receptors has also been shown to reduce yawning.
Thus, the released dopamine may inhibit yawning
through D1 receptor activation.

Overall, whether the activation of adrenergic
system inhibited the release of acetylcholine or
directly interacted with cholinergic mechanisrns
involved in yawning it is not presently clear,
and should be examined further. Prazosin,
phenoxybenzamine, and propranolol by themselves
did not change physostigmine-induced yawning.
Therefore, the negative influence of the brain
adrenergic mechanism(s) on the yawning behavior
seems unlikely. However, il has been proposed
that beta-adrenoceptor antagonists are able to
increase yawning induced by cholinergie and
doparninergic drugs.